The long term objectives are to understand the functions of specialized membrane organelles of plasmodia, their interactions with the host and how they can be exploited to effectively deliver drugs to the organism. The specific aims are to identify and characterize parasite activities which underlie tubular and vesicular trafficking in the erythrocyte cytosol and are directly relevant to understanding intracellular membrane traffic in eukaryotes and how the parasite imports extracellular nutrients across the cytoplasm and membrane of the red cell. In the asexual blood stages plasmodium has a complex relationship with its host which is poorly understood at both the biochemical and the structural level. The use of microscopic, biochemical and molecular biological tools to analyze cellular parasite phenomena should elucidate relevant modes of host-parasite interaction. In general, mechanisms for the regulation of transport pathways are conserved in cells. There is evidence for the directed transport of plasmodial proteins to the cytosol and membrane of the infected erythrocyte which results in modifications in the structure and functions of the host cell. Functional similarities between plasmodial activities and those which regulate membrane transport in higher cells suggest approaches to investigate trafficking events in plasmodium. The in vitro cultivation of plasmodium falciparum permits these studies in human malaria. Relatively large amounts of parasites can be grown in the laboratory to generate adequate quantities of RNA, DNA and immunopurified radiolabelled proteins. cDNA, genomic or protein structure can then be investigated by chemical and enzymatic methods to determine specific aspects of primary structure or modifications thereof, which promote membrane transport in the rod cell. The use of specific antibodies to localize protein components by microscopy and kinetic analyses of the biosynthesis and turnover of these proteins (by immunoprecipitation of the polypeptides in pulse chase studies) enables determining their true location and the pathways of transport in the cell. The project will provide a comprehensive, mechanistic study of tubovesicular traffic induced in red cells by plasmodium.